Synthesis and Structure Elucidation of New NSAID Diphosphine Ruthenium(II) Complexes as Potential Anticancer Agents: DNA/BSA Binding and Cytotoxicity Assays

Abstract

New diphosphine ruthenium(II) complexes with nonsteroidal anti-inflammatory drugs (NSAID) derivatives with general formula [Ru(L)(dppe)2]PF6 [dppe = 1,2-bis(diphenylphosphine)ethane and (L) corresponds to fenamate (fe–) (Complex 1), mefenamate (me–) (Complex 2), tolfenamate (tol–) (Complex 3) or flufenamate (flu–) (Complex 4)] were synthesized. All compounds were characterized by several techniques, including 1H, 13C{1H} and 31P{1H} NMR, cyclic voltammetry, conductivity, elemental analysis, ultraviolet/visible absorption spectroscopy, infrared absorption spectroscopy and single crystal X-ray diffraction. ct-DNA (Calf-Thymus DNA) interaction studies by spectroscopic titrations and viscosity measurements demonstrated that the complexes may interact weakly with ct-DNA, considering that the complexes are cationic and that DNA carries a negative charge due to its phosphate groups, electrostatic interactions could occur. The complexes showed a moderate interaction with Bovine Serum Albumin (BSA) mediated by both dynamic and static quenching mechanisms. Also, the cytotoxic activity of the complexes was evaluated against breast (MDA-MB-231) and lung (A549) tumor cell lines and nontumor lung (MRC-5) cell lines. All complexes showed cytotoxicity against the cell lines investigated, with IC50 values in the range of 0.94–17.71 μM. [Ru(me)(dppe)2]PF6 showed a high selectivity index against the A549 cell line. For MDA-MB-231 cell line, the most selective complex was [Ru(fe)(dppe)2]PF6. Except for [Ru(tol)(dppe)2]PF6, all other complexes were more cytotoxic than cisplatin, making them promising compounds.